Hypertension Nephropathy Complex
Diabetes remains the leading cause of end-stage renal disease (ESRD) in most countries worldwide, accounting for 40–50% of incident ESRD cases. Owing to the epidemic of diabetes secondary to obesity and the ageing of the population, these rates are only predicted to rise. The natural history of diabetic renal disease, despite being the subject of systematic studies for over 70 years, remains poorly understood.
The condition is believed to pass through arbitrary stages of escalating albuminuria associated with a parallel rise in blood pressure and fall in glomerular filtration rate (GFR) evolving eventually to ESRD. It is generally considered that once overt diabetic nephropathy, manifesting as persistent proteinuria, is present, it is only possible to slow, but not halt, the progression towards ESRD. Early predictors were therefore sought and the emphasis shifted to an earlier stage of abnormal albuminuria that is not detectable by routine laboratory methods. This stage of incipient nephropathy, characterised as microalbuminuria (MA), has been defined as the excretion of 30–300mg of urinary albumin per 24-hour period or equivalent spot urinary albumin/creatinine ratio (ACR) of 3.5–30mg/mmol. In prospective studies, such levels of albumin excretion have been shown to indicate an increased risk of overt nephropathy in patients with type 1 and type 2 diabetes. There has been widespread acceptance of MA as being the best and the earliest available non-invasive marker of diabetic renal disease leading to a number of recommendations advocating its routine screening. There are, however, several disadvantages with this approach.
Pitfalls of MA Screening
Most importantly, there has been no long-term study evaluating the effectiveness of MA screening nor has there been any published comprehensive metaanalysis of the available studies looking at the prognostic significance of MA. The predictive value of MA for overt nephropathy is also in question. While earlier studies suggested high progression rates (85–100%) to overt nephropathy, recent literature seems to suggest much less progression (20–30%) with the vast majority of patients with baseline MA shown to either regress or persist even after many years of follow up. There is also no convincing evidence of a graded relationship between the level of albuminuria and the extent of renal structural damage. Albuminuria is not unique to diabetic renal disease and there are a number of potential confounders that can affect the level of urine albumin, including some physiological and reversible causes (prolonged standing, exercise, etc.), creating problems with its interpretation. Furthermore, albuminuria has not always been shown to be a pre-requisite for the presence or progression of proven diabetic glomerulosclerosis. Studies involving type 1 and type 2 diabetes patients report 20–30% prevalence of normoalbuminuric renal impairment secondary to diabetic nephropathy. The rate of decline in GFR have been shown to be unrelated to the albuminuria status. Doubts therefore remain on whether the presence of MA genuinely confers a greater risk and more importantly, whether the lack of it confers a good outlook.